A series of transplantable murine colon tumours has been developed from dimethylhydrazine induced primary tumours. They appear to be of value as chemotherapy screening models and have a range of sensitivities to 5-fluorouracil treatment. The object of the project is to use the model to investigate biochemical, cell kinetic and pharmacokinetic factors determining sensitivity of the series of transplant lines to 5-fluorouracil with the aim of using such knowledge to predict the sensitivity of human tumours prior to therapy. Cell kinetic parameters of the tumours and the levels of a number of enzymes known to be involved in 5-fluorouracil metabolism will be determined. The pharmacokinetics of fluorouracil and its active metabolite fluorodeoxyuridylic acid will be determined using high pressure liquid chromatography and enzymatic assays. Attempts will be made to correlate these various parameters with sensitivity to the drug. Any significant correlations will be tested in human tumour xenograft transplant lines in immunosuppressed mice. Methods will then be developed to allow a predictive test of sensitivity to be made on biopsy specimens using both animal systems as models.